Iron deficiency anemia (IDA) is frequently seen in inflammatory bowel disease. Traditionally, oral iron supplementation is linked to extensive gastrointestinal side effects and possible disease ...exacerbation. This multicenter phase-3 study tested the efficacy and safety of ferric maltol, a complex of ferric (Fe) iron with maltol (3-hydroxy-2-methyl-4-pyrone), as a novel oral iron therapy for IDA.
Adult patients with quiescent or mild-to-moderate ulcerative colitis or Crohn's disease, mild-to-moderate IDA (9.5-12.0 g/dL and 9.5-13.0 g/dL in females and males, respectively), and documented failure on previous oral ferrous products received oral ferric maltol capsules (30 mg twice a day) or identical placebo for 12 weeks according to a randomized, double-blind, placebo-controlled study design. The primary efficacy endpoint was change in hemoglobin (Hb) from baseline to week 12. Safety and tolerability were assessed.
Of 329 patients screened, 128 received randomized therapy (64 ferric maltol-treated and 64 placebo-treated patients) and comprised the intent-to-treat efficacy analysis: 55 ferric maltol patients (86%) and 53 placebo patients (83%) completed the trial. Significant improvements in Hb were observed with ferric maltol versus placebo at weeks 4, 8, and 12: mean (SE) 1.04 (0.11) g/dL, 1.76 (0.15) g/dL, and 2.25 (0.19) g/dL, respectively (P < 0.0001 at all time-points; analysis of covariance). Hb was normalized in two-thirds of patients by week 12. The safety profile of ferric maltol was comparable with placebo, with no impact on inflammatory bowel disease severity.
Ferric maltol provided rapid clinically meaningful improvements in Hb and showed a favorable safety profile, suggesting its possible use as an alternative to intravenous iron in IDA inflammatory bowel disease.
Visceral adipose tissue (VAT) could affect Crohn's disease (CD); however, no prospective clinical studies have explored the issue.
We measured VAT with magnetic resonance imaging and total fat mass ...(FM) with air-displacement plethysmography in 31 women with CD in remission and 19 matched control women. We assessed the VAT/FM ratio as index of VAT accumulation, measured cytokines, and monitored clinical features (duration of remission, disease behavior, and outcome) in patients with CD retrospectively and prospectively. We also tested whether ultrasound could provide a surrogate marker of VAT in patients with CD.
Patients with CD had higher percentage of FM (37 ± 10% versus 31 ± 10%, P = 0.03), VAT (1885 ± 1403 mL versus 941 ± 988 mL, P = 0.02), and VAT/FM ratio (65 ± 24 mL/kg versus 37 ± 25 mL/kg, P = 0.004) than control women. In patients with CD, VAT/FM ratio was associated with leptin (P = 0.009) and interleukin 6 (P = 0.032) concentrations, and higher in short-term than in long-term remission (72.6 ± 27.1 mL/kg versus 54.8 ± 16.1 mL/kg, P = 0.079). Patients with CD with stricturing/fistulizing disease had a higher VAT/FM ratio than patients with nonstricturing/nonfistulizing behavior (79 ± 0.15 mL/kg versus 63 ± 28 mL/kg, P = 0.067). A higher baseline VAT/FM ratio was associated with an increased disease activity at follow-up (P = 0.029). The ultrasound-determined thickness between the abdominal wall and the aorta was strongly associated with VAT as measured by magnetic resonance imaging (P < 0.001).
VAT accumulation could be a prospective risk factor for increased disease activity in CD.
Hepatitis E–induced severe myositis Mengel, Annerose M.; Stenzel, Werner; Meisel, Andreas ...
Muscle & nerve,
February 2016, 2016-Feb, 2016-02-00, 20160201, Letnik:
53, Številka:
2
Journal Article
Recenzirano
ABSTRACT
Introduction
Hepatitis E virus (HEV) is endemic in Asian and African countries but is rarely reported in Western countries. Although there are some prominent neurological manifestations, HEV ...is rarely recognized by neurologists.
Methods
This is a case report of myositis induced by HEV.
Results
We report the life‐threatening case of a 57‐year‐old man with flaccid tetraparesis due to myositis, acute hepatitis, and renal failure caused by HEV infection. Muscle biopsy revealed scattered myofiber necrosis with a diffuse, mild lymphomonocytic infiltrate in the endomysium and perimysium. Because the patient suffered from an acute HEV infection with a rapidly progressive course of severe myopathy, we started ribavirin treatment. He recovered partially within 3 weeks and recovered fully within 6 months.
Conclusion
This case highlights a neurological manifestation of endemic HEV infection with severe myositis in a patient with alcoholic chronic liver disease. Ribavirin treatment is effective in severe HEV infection and may also lead to rapid neurological recovery. Muscle Nerve 53: 317–320, 2016
Smoking worsens Crohn's disease (CD). The aryl hydrocarbon receptor (AhR) is a transcription factor that mediates the toxicity of dioxinlike chemicals. We hypothesized that AHR variants and smoking ...influence CD.
Exon-intron boundaries and coding and promoter regions of AHR gene were sequenced (28 patients with inflammatory bowel disease; 4 healthy controls). Two identified variants (rs7796976 and rs2066853) were studied for an association with intestinal permeability (IP, oral sugar test) in patients with inflammatory bowel disease (stratified according to the smoking status). AHR expression was analyzed by quantitative real-time polymerase chain reaction in colonic biopsies from patients with CD (n = 53). Case-control analysis including a genotype-phenotype correlation was performed for both variants (n = 767 patients with inflammatory bowel disease; n = 466 healthy controls).
Sequencing identified a putative promoter variant (rs7796976) and a nonsynonymous variant (rs2066853; Arg554Lys) in AHR, both predicted to be functionally relevant. The major G-allele of rs7796976 increased the risk for disturbed IP (odds ratio 1.9, 95% confidence interval CI, 1.1-3.2) in CD but not ulcerative colitis. We observed an additive effect of the rs7796976 genotype and smoking on IP (P = 0.005), which was also shown for rs2066853 (P = 0.004; variants not linked). Both variants showed a genotype-dependent AHR expression in colonic biopsies of patients with CD. No overall association with either CD or ulcerative colitis was observed; however, the rs7796976 genotype and smoking increased the risk for the L4 phenotype in CD.
Smoking and functionally relevant AHR variants increase IP in CD. Because AhR is known to mediate between smoking and inflammation, these variants might be involved in the deleterious effect of smoking on CD.
Abstract Objective This prospective, controlled, and multicentric study evaluated nutritional status, body composition, muscle strength, and quality of life in patients with inflammatory bowel ...disease in clinical remission. In addition, possible effects of gender, malnutrition, inflammation, and previous prednisolone therapy were investigated. Methods Nutritional status (subjective global assessment SGA, body mass index, albumin, trace elements), body composition (bioelectrical impedance analysis, anthropometry), handgrip strength, and quality of life were assessed in 94 patients with Crohn's disease (CD; 61 female and 33 male, Crohn's Disease Activity Index 71 ± 47), 50 patients with ulcerative colitis (UC; 33 female and 17 male, Ulcerative Colitis Activity Index 3.1 ± 1.5), and 61 healthy control subjects (41 female and 20 male) from centers in Berlin, Vienna, and Bari. For further analysis of body composition, 47 well-nourished patients with inflammatory bowel disease were pair-matched by body mass index, sex, and age to healthy controls. Data are presented as median (25th–75th percentile). Results Most patients with inflammatory bowel disease (74%) were well nourished according to the SGA, body mass index, and serum albumin. However, body composition analysis demonstrated a decrease in body cell mass (BCM) in patients with CD (23.1 kg, 20.8–28.7, P = 0.021) and UC (22.6 kg, 21.0–28.0, P = 0.041) compared with controls (25.0 kg, 22.0–32.5). Handgrip strength correlated with BCM ( r = 0.703, P = 0.001) and was decreased in patients with CD (32.8 kg, 26.0–41.1, P = 0.005) and UC (31.0 kg, 27.3–37.8, P = 0.001) compared with controls (36.0 kg, 31.0–52.0). The alterations were seen even in patients classified as well nourished. BCM was lower in patients with moderately increased serum C-reactive protein levels compared with patients with normal levels. Conclusion In CD and UC, selected micronutrient deficits and loss of BCM and muscle strength are frequent in remission and cannot be detected by standard malnutrition screening.
Abstract Objective Adipokines are fat-derived hormones and cytokines with immune-modulating and metabolic properties. Most of them are associated with insulin resistance. The aim of the present ...investigation was to evaluate circulating levels of adipokines and glucose homeostasis in patients with inflammatory bowel disease (IBD) and to evaluate possible associations with the course and characteristics of the disease. Methods Serum leptin, resistin, visfatin, retinol-binding protein-4, adiponectin, glucose, insulin, and inflammatory parameters were analyzed in 93 patients with inactive IBD (49 with Crohn's disease CD, 44 with ulcerative colitis UC), 35 patients with active IBD (18 with CD, 17 with UC), and 37 age- and body mass index–matched healthy controls. Ninety-two patients were followed for 6 mo. Results Leptin was similar in patients with IBD and controls, whereas resistin and visfatin were increased in patients with active disease but not in those in remission. In active and inactive disease, adiponectin was decreased ( P < 0.001) and retinol-binding protein-4 was increased ( P < 0.001) compared with controls. About 60% of patients with IBD showed increased levels of insulin, whereas serum glucose remained normal, resulting in increased homeostasis model assessment values in most patients. Hyperinsulinemia was associated with the decrease in adiponectin ( r = −0.572, P < 0.001) and proved to be an independent protective factor for 6-mo maintenance of remission ( P = 0.016). Conclusion IBD led to largely similar alterations in circulating adipokines and hyperinsulinemia in patients with CD and those with UC. The unexpected protective effect of hyperinsulinemia on relapse rate denotes the role of the metabolic–inflammatory response as a modulator in IBD.
PEPT1 was proposed to be expressed only in inflamed colonic tissues in which it could contribute to inflammatory bowel disease (IBD) development by transporting bacterial peptides, such as muramyl ...dipeptide (MDP), that activate intracellular pattern recognition receptors, such as the nucleotide-binding and oligomerization domain 2. To better define the pathological relevance of this transporter, we analyzed PEPT1 expression during intestinal inflammation and studied the susceptibility of Pept1-deficient (Pept1) mice to experimental colitis.
Wild-type and Pept1 mice were treated with dextran sulfate sodium and 2,4,6-trinitrobenzene sulfonic acid to induce colitis, and MDP-induced cytokine expression was studied in colonic tissue cultures. PEPT1 expression was characterized in mouse models of Crohn's disease-like ileitis (Tnf) or colitis (Il-10, Il-10XTlr2) and endoscopic tissue samples from descending colon of patients with IBD (n = 11) and controls (n = 17). Moreover, the prevalence of the PEPT1 single-nucleotide polymorphism rs2297322 was tested in German patients with IBD (n = 458) and controls (n = 452).
PEPT1 expression was consistently reduced under condition of acute or chronic experimental inflammation. Wild-type and Pept1 mice revealed comparable susceptibility to dextran sulfate sodium-induced and 2,4,6-trinitrobenzene sulfonic acid-induced colitis, and MDP-induced cytokine expression was PEPT1-independent. PEPT1 expression levels were also decreased in descending colon of patients with IBD during acute inflammation, but the rs2297322 single-nucleotide polymorphism was not associated with IBD susceptibility in the German cohort.
PEPT1 expression is reduced during intestinal inflammation and PEPT1 is neither required for MDP-induced immune response nor is the PEPT1 rs2297322 single-nucleotide polymorphism associated with IBD susceptibility in our German cohort. These data strongly argue against a primary role of PEPT1 in the initiation or progression of IBD.
Summary
Human longevity is characterized by a remarkable lack of confirmed genetic associations. Here, we report on the identification of a novel locus for longevity in the RAD50/IL13 region on ...chromosome 5q31.1 using a combined European sample of 3208 long‐lived individuals (LLI) and 8919 younger controls. First, we performed a large‐scale association study on 1458 German LLI (mean age 99.0 years) and 6368 controls (mean age 57.2 years) by targeting known immune‐associated loci covered by the Immunochip. The analysis of 142 136 autosomal single nucleotide polymorphisms (SNPs) revealed an Immunochip‐wide significant signal (PImmunochip = 7.01 × 10–9) for the SNP rs2075650 in the TOMM40/APOE region, which has been previously described in the context of human longevity. To identify novel susceptibility loci, we selected 15 markers with PImmunochip < 5 × 10–4 for replication in two samples from France (1257 LLI, mean age 102.4 years; 1811 controls, mean age 49.1 years) and Denmark (493 LLI, mean age 96.2 years; 740 controls, mean age 63.1 years). The association at SNP rs2706372 replicated in the French study collection and showed a similar trend in the Danish participants and was also significant in a meta‐analysis of the combined French and Danish data after adjusting for multiple testing. In a meta‐analysis of all three samples, rs2706372 reached a P‐value of PImmunochip+Repl = 5.42 × 10−7 (OR = 1.20; 95% CI = 1.12–1.28). SNP rs2706372 is located in the extended RAD50/IL13 region. RAD50 seems a plausible longevity candidate due to its involvement in DNA repair and inflammation. Further studies are needed to identify the functional variant(s) that predispose(s) to a long and healthy life.
Background/Aims: Standard treatments are not available for hilar nonresectable cholangiocarcinoma (NCC). It is unknown whether combination therapy of photodynamic therapy (PDT) plus systemic ...chemotherapy is superior to PDT alone. Methods: We retrospectively reviewed 68 patients with hilar NCC treated with either PDT plus chemotherapy (PTD-C) or PDT monotherapy (PDT-M). The primary endpoint was the mean overall survival rate. Secondary endpoints included the 1-year survival rate, risk of cholangitic complications, and outcomes, which were evaluated according to the chemotherapy protocol. Results: More than 90% of the study population had advanced hilar NCC Bismuth type III or IV. In the PDT-M group (n=35), the mean survival time was 374 days compared with 520 days in the PDT-C group (n=33, p=0.021). The 1-year survival rate was significantly higher in the PDT-C group compared with the PDT-M group (88% vs 58%, p=0.001) with a significant reduction of mortality (hazard ratio, 0.20; 95% confidence interval, 0.07 to 0.58; p=0.003). Gemcitabine monotherapy resulted in a shorter survival time compared with the gemcitabine combination therapy (mean, 395 days vs 566 days; p=0.09). Cholangitic complications were observed at a similar frequency in the PDT-C and PDT-M groups. Conclusions: Combining repeated PDT with a gemcitabine-based combination therapy might offer a significant survival benefit in patients with hilar NCC. (Gut Liver 2016;10:470-475)
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